PROJECT SUMMARY/ ABSTRACT This K01 career development award applicant is trained as a genetic epidemiologist and his research has genome wide association studies (GWAS) of gastrointestinal diseases such as colorectal adenoma and gallstone disease. He recently led a study that identified novel genetic markers of gallstone disease in a GWAS meta-analyses within 10 international cohorts. In this proposal, the candidate seeks to continue his work on gallbladder disease, and work on application of knowledge from `omic' studies, into the clinic for individualized patient care. He plans to develop metabolomics based biomarkers to predict the risk of symptomatic gallbladder disease. He will then determine their clinical effectiveness in predicting persistence of symptoms in cholecystectomy patients, and the cost-effectiveness of these biomarker tools using mathematical simulation models. The overarching hypothesis of this proposal is that metabolomic signatures can accurately distinguish patients with biliary-type pain that are more likely to benefit from cholecystectomy from those for whom cholecystectomy may be unnecessary. This proposal will allow him to expand his training from the population-based setting to patient oriented research, and gain experience in comparative effectiveness analyses. To complete this proposal, the candidate will require additional training in the areas of decision sciences, patient oriented research and metabolomics. He will benefit from a multidisciplinary mentoring committee, consisting of internationally recognized experts in gastroenterology, clinical epidemiology, health decision sciences, biomarker epidemiology, and metabolomics. His training plan, developed with close supervision of his mentoring committee, will include didactic coursework at HSPH with the objective to gain fluency with key concepts in these training areas. The candidate's primary mentor Dr. Andrew T. Chan has an established track record of effectively mentoring fellows and junior faculty towards successful academic careers. His research advisory committee will not only provide methodological expertise, but also mentoring support, guidance and critical focused so far on gene-environment interactions in the risk of cancers, and feedback to ensure the candidate's transition towards independence . The research environment, which includes MGH Clinical and Translational Epidemiology Unit, MGH Division of Gastroenterology, the Channing Division of Network Medicine, The Harvard Clinical and Translational Science Center and the Harvard T H Chan School of Public Health will provide vast collaborative resources, relevant advanced course-work, seminars and other didactic training opportunities for the candidate during this critical developmental period. Through this award, the candidate will realize his long term goal of becoming an independent translational investigator, and establishing a research program in a clinical setting, with specific focus on gastrointestinal diseases.